Abstract Introduction Sleep disturbances are common after surgery and can negatively affect recovery, leading to greater pain, delirium, cardiovascular events, and longer hospital stays. Improving sleep quality during the postoperative period has therefore become an important focus in perioperative care. Esketamine, an NMDA-receptor antagonist has been proposed to modulate sleep architecture and improve rest after surgery. However, findings from clinical trials have been inconsistent. This meta-analysis integrates the latest randomized evidence to clarify the role of esketamine in improving postoperative sleep quality and recovery while assessing its safety profile. Methods This meta-analysis followed Cochrane and PRISMA guidelines. A systematic literature search was conducted in PubMed, Scopus, and the Cochrane Library to identify randomized controlled trials (RCTs) evaluating the role of esketamine in postoperative sleep, covering publications up to october 2025.Two independent reviewers screened the 372 initially identified records, assessing titles and abstracts for eligibility. Full-text articles meeting the inclusion criteria were subsequently reviewed. Any discrepancies were resolved by consensus or by consulting a third reviewer. Heterogeneity among studies was assessed using I² statistics. Results Thirty-one RCTs including 3443 patients were analyzed. Esketamine significantly improved postoperative sleep quality on postoperative day (POD) 1 (mean difference MD −1.05; 95% CI − 1.71 to − 0.39; p = 0.002) and POD3 (MD − 0.72; 95% CI − 0.84 to − 0.61; p 0.00001), with benefits persisting across follow-up assessments. Esketamine also reduced the need for additional postoperative analgesics, suggesting an analgesic-sparing effect. Safety outcomes were favorable: no increased risk of nausea or vomiting (OR 1.03; 95% CI 0.85-1.25; p = 0.77), and no excess of neuropsychiatric effects such as nightmares or hallucinations (OR 1.41; 95% CI 0.65-3.04; p = 0.38). No serious adverse events attributable to esketamine were reported. Conclusion Esketamine improves postoperative sleep quality and reduces analgesic requirements without increasing adverse or neuropsychiatric events, supporting its favorable safety and efficacy profile in perioperative care. These results strengthen the evidence for esketamine as a potential adjunct to enhance postoperative recovery and patient-centered outcomes, while long-term data are warranted to define its optimal role and dosing strategies. This abstract is funded by: None
Lúcio et al. (Fri,) studied this question.